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Small-molecule PET Tracers for Imaging Proteinopathies
Mathis CA, Lopresti BJ, Ikonomovic MD, Klunk WE.. Seminars in nuclear medicine, 2017-07-13
Topic: Brain proteins, microglia and lab models
In this chapter, we provide a review of the challenges and advances in developing successful PET imaging agents for 3 major types of aggregated amyloid proteins: amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn). These 3 amyloids are involved in the pathogenesis of a variety of neurodegenerative diseases, referred to as proteinopathies or proteopathies, that include Alzheimer disease, Lewy body dementias, multiple system atrophy, and frontotemporal dementias, among others. In the Introduction section, we briefly discuss the history of amyloid in neurodegenerative diseases and describe why progress in developing effective imaging agents has been hampered by the failure of crystallography to provide definitive ligand-protein interactions for rational radioligand design efforts. Instead, the field has relied on largely serendipitous, trial-and-error methods to achieve useful and specific PET amyloid imaging tracers for Aβ, tau, and α-syn deposits. Because many of the proteopathies involve more than 1 amyloid protein, it is important to develop selective PET tracers for the different amyloids to help assess the relative contribution of each to total amyloid burden. We use Pittsburgh compound B to illustrate some of the critical steps in developing a potent and selective Aβ PET imaging agent. Other selective Aβ and tau PET imaging compounds have followed similar pathways in their developmental processes. Success for selective α-syn PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories throughout the world. In the tau sections, we provide background regarding 3-repeat (3R) and 4-repeat (4R) tau proteins and how they can affect the binding of tau radioligands in different tauopathies. We review the ongoing efforts to assess the properties of tau ligands, which are useful in 3R, 4R, or combined 3R-4R tauopathies. Finally, we describe in the α-syn sections recent attempts to develop selective tracers to image α-synucleinopathies.
Key findings
- Other selective Aβ and tau PET imaging compounds have followed similar pathways in their developmental processes.
- Success for selective α-syn PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories throughout the world.
- In the tau sections, we provide background regarding 3-repeat (3R) and 4-repeat (4R) tau proteins and how they can affect the binding of tau radioligands in different tauopathies.
- We review the ongoing efforts to assess the properties of tau ligands, which are useful in 3R, 4R, or combined 3R-4R tauopathies.
- Finally, we describe in the α-syn sections recent attempts to develop selective tracers to image α-synucleinopathies.
Why it matters
Developing selective PET tracers for different amyloid proteins is important because many proteopathies involve more than one amyloid protein, and selective tracers could help assess each protein's relative contribution to total amyloid burden. Success for selective alpha-synuclein PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories.
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Study details
- Evidence strengthLow
How this study scored 42/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Seminars in nuclear medicine) |
| Journal's citation record | 1 / 4 | Seminars in Nuclear Medicine: journal h-index 127 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2017 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 5 / 7 | Cited 123 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.2 citations a year over 11 year(s) since 2017 |
| Impact for its field and year | 3 / 6 | Cited 7.9× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 1 / 6 | Cited by 2 other studies in this library |
| Still being cited | 2 / 4 | Cited 30 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author William E. Klunk: h-index 108 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pittsburgh: institution h-index 1,470 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 28826526) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 42 / 100 | — |
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Read the original
- DOI: 10.1053/j.semnuclmed.2017.06.003
- PubMed: 28826526
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Mathis, C. A., Lopresti, B. J., Ikonomovic, M. D., & Klunk, W. E. (2017). Small-molecule PET Tracers for Imaging Proteinopathies. Seminars in nuclear medicine. https://doi.org/10.1053/j.semnuclmed.2017.06.003
Vancouver
Mathis CA, Lopresti BJ, Ikonomovic MD, Klunk WE. Small-molecule PET Tracers for Imaging Proteinopathies. Seminars in nuclear medicine. 2017. doi:10.1053/j.semnuclmed.2017.06.003. PMID: 28826526.
BibTeX
@article{mathis2017-28826526,
author = {Mathis, C. A. and Lopresti, B. J. and Ikonomovic, M. D. and Klunk, W. E.},
title = {{Small-molecule PET Tracers for Imaging Proteinopathies}},
journal = {Seminars in nuclear medicine},
year = {2017},
doi = {10.1053/j.semnuclmed.2017.06.003},
pmid = {28826526},
url = {https://doi.org/10.1053/j.semnuclmed.2017.06.003}
}
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